The molybdenum cofactor common to all molybdoenzymes except nitrogenase has been isolated in an inactive form in this laboratory and shown to contain a pterin moiety. The complete structure of the cofactor remains to be elucidated. Once the complete structure is known, attempts will be directed at restoring the functional competence of the cofactor. Since the cofactor appears to be the same in E. coli and in animals the biosynthesis of the cofactor will be investigated using E. coli and/or experimental animals. To this end isolation of E. coli mutants deficient in cofactor will be attempted. The identification so far of 3 human patients with apparent cofactor deficiency has raised the question of the manner of assimilation of the cofactor by human cells. This will be investigated using fibroblasts from normal and deficient patients. The reason for the absence of sulfite oxidase CRM in the cells of cofactor-deficient patients will also be probed.